IDH-mutant astrocytomas with primitive neuronal component have a distinct methylation profile and a higher risk of leptomeningeal spread
IDH-mutant astrocytomas are diffuse gliomas that are defined by characteristic mutations in IDH1 or IDH2 and do not have complete 1p/19q co-deletion. The established grading criteria include histological features of brisk mitotic activity (grade 3) and necrosis and/or microvascular proliferation (gr...
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
03 February 2025
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| In: |
Acta neuropathologica
Year: 2025, Jahrgang: 149, Pages: 1-13 |
| ISSN: | 1432-0533 |
| DOI: | 10.1007/s00401-025-02849-8 |
| Online-Zugang: | Resolving-System, kostenfrei, Volltext: https://dx.doi.org/10.1007/s00401-025-02849-8
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| Verfasserangaben: | Felix Hinz, Dennis Friedel, Andrey Korshunov, Franziska M. Ippen, Henri Bogumil, Rouzbeh Banan, Sebastian Brandner, Martin Hasselblatt, Henning B. Boldt, Vaidas Dirse, Hildegard Dohmen, Eleonora Aronica, Michael Brodhun, Marike L.D. Broekman, David Capper, Asan Cherkezov, Maximilian Y. Deng, Vera van Dis, Jörg Felsberg, Stephan Frank, Pim J. French, Rüdiger Gerlach, Kirsten Göbel, Eric Goold, Jürgen Hench, Sven Kantelhardt, Patricia Kohlhof-Meinecke, Sandro Krieg, Christian Mawrin, Gillian Morrison, Angelika Mühlebner, Koray Ozduman, Stefan M. Pfister, Pietro Luigi Poliani, Marco Prinz, Guido Reifenberger, Markus J. Riemenschneider, Roman Sankowski, Daniel Schrimpf, Martin Sill, Matija Snuderl, Robert M. Verdijk, Mathew R. Voisin, Pieter Wesseling, Wolfgang Wick, David E. Reuss, Andreas von Deimling, Felix Sahm, Sybren L.N. Maas, Abigail K. Suwala |
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| 245 | 1 | 0 | |a IDH-mutant astrocytomas with primitive neuronal component have a distinct methylation profile and a higher risk of leptomeningeal spread |c Felix Hinz, Dennis Friedel, Andrey Korshunov, Franziska M. Ippen, Henri Bogumil, Rouzbeh Banan, Sebastian Brandner, Martin Hasselblatt, Henning B. Boldt, Vaidas Dirse, Hildegard Dohmen, Eleonora Aronica, Michael Brodhun, Marike L.D. Broekman, David Capper, Asan Cherkezov, Maximilian Y. Deng, Vera van Dis, Jörg Felsberg, Stephan Frank, Pim J. French, Rüdiger Gerlach, Kirsten Göbel, Eric Goold, Jürgen Hench, Sven Kantelhardt, Patricia Kohlhof-Meinecke, Sandro Krieg, Christian Mawrin, Gillian Morrison, Angelika Mühlebner, Koray Ozduman, Stefan M. Pfister, Pietro Luigi Poliani, Marco Prinz, Guido Reifenberger, Markus J. Riemenschneider, Roman Sankowski, Daniel Schrimpf, Martin Sill, Matija Snuderl, Robert M. Verdijk, Mathew R. Voisin, Pieter Wesseling, Wolfgang Wick, David E. Reuss, Andreas von Deimling, Felix Sahm, Sybren L.N. Maas, Abigail K. Suwala |
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| 520 | |a IDH-mutant astrocytomas are diffuse gliomas that are defined by characteristic mutations in IDH1 or IDH2 and do not have complete 1p/19q co-deletion. The established grading criteria include histological features of brisk mitotic activity (grade 3) and necrosis and/or microvascular proliferation (grade 4). In addition, homozygous deletion of the CDKN2A/B locus has recently been implemented as a molecular marker for grade 4 IDH-mutant astrocytomas. Here, we describe a subgroup of high-grade IDH-mutant astrocytomas characterised by a primitive neuronal component based on histology and a distinct DNA methylation profile (n = 51, ASTRO PNC). Misinterpretation as carcinoma metastasis was common, since GFAP expression was absent in the primitive neuronal component, whereas TTF-1 expression was detected in 15/19 cases (79%) based on immunohistochemistry. Apart from mutations in IDH1, TP53, and ATRX, we observed enrichment for alterations in RB1 (n = 19/51, 37%) and MYCN (n = 14/51, 27%). Homozygous CDKN2A/B deletion (n = 1/51, 2%) and CDK4 amplification (n = 3/51, 6%) were relatively rare events. Clinical (n = 31 patients) and survival data (n = 23 patients) indicate a clinical behaviour similar to other CNS WHO grade 4 IDH-mutant astrocytomas, however with an increased risk for leptomeningeal (n = 7) and extra-axial (n = 2) spread. Taken together, ASTRO PNC is defined by a distinct molecular and histological appearance that can mimic metastatic disease and typically follows an aggressive clinical course. | ||
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